Endobronchial lung volume reduction (ELVR) may be helpful in a selected group of patients with advanced stages of emphysema. However, collateral ventilation (CV) from adjacent lobes through collateral channels often prevents target lobe atelectasis, which presumably mediates clinical responses after ELVR. With the goal of identifying patients who are more or less likely to benefit, we propose endobronchial CV assessment (ECVA), a novel catheter-based endobronchial approach, to quantitatively determine the resistance of collateral channels ( R coll). ECVA relies on the measurement of spontaneous airflow from the sealed and isolated target compartment during spontaneous respiration in an awake subject, thereby providing a direct, simple, and minimally invasive method of assessing R coll in lungs. In this study, we validated ECVA in a controlled laboratory setup and tested ECVA's clinical feasibility in 11 emphysematous human subjects undergoing ELVR treatment. To evaluate ECVA in a controlled laboratory setup with known CV levels, we built a benchtop model mimicking a simple one-compartment model of the lungs during temporary compartmental occlusion and spontaneous respiration, which could be adapted to hold restrictors of different sizes representing collateral airways, and applied ECVA to estimate the resistance of various benchtop model restrictors. We then rated ECVA's performance by direct comparison between estimated and actual restrictor resistance and found a correlation coefficient near one. To test ECVA's clinical performance, post-ELVR radiological assessments were made to determine the occurrence of atelectasis in the treated lobe, and interlobar R coll was estimated in the target lobe via ECVA pre-ELVR. ECVA could be completed in all patients with no adverse events, and a high R coll by ECVA predicted absorption atelectasis following ELVR ( P = 0.005). We believe that ECVA may be helpful to distinguish those patients with and without interlobar CV by identifying the critical value of R coll above which atelectasis is likely to occur.